Skin inflammation and aging are closely related phenomena. So similar are the processes involved with both, that aging is sometimes described dermatologically as a chronic low grade inflammatory condition. Both inflammation and aging are initiated in part by free radical damage, which takes place mostly within the cell membrane. The cell membrane is most susceptible to attack by free radicals because of its higher oxygen tension in comparison with the cotysol and its dense molecular structure largely comprising lipids and lipoproteins, which are easily oxidized by reactive oxygen species such as singlet oxygen, the superoxide anion, and hydroxyl radicals. These and other free radicals are generated in normal metabolism, as well as through ultraviolet sun exposure, exposure to other forms of ionizing and non-ionizing radiation, environmental factors such as pollution or exposure to chemicals in the home or workplace, and stresses such as infection or extreme exercise. The body's endogenous antioxidant defense systems made up of antioxidants such as vitamins C and E, glutathione, and enzymes, e.g., superoxide dismutase, are overwhelmed.
In the body's response, proinflammatory and inflammatory cascades are activated which cause the formation of toxic intermediates and end products, resulting in further, continuous, and ultimately greater damage than that caused by the initial transient reactive species. Transcription factors such as NFκB and AP1 are activated, which in turn cause production of proinflammatory mediators. These mediators, called cytokines, such as tumor necrosis factor α (TNFα) and various interleukins, cause a burst of free radicals. Arachadonic acid is released, which is itself toxic, and it is oxidized to biologically active mediators. When arachadonic acid is oxidized via the cyclooxygenase or lipoxygenase pathways, for example, prostaglandins, leukotrines, and hyroxyeicosatetraenoic acid (HETE) are produced, which cause erythma, edema, and additional free radical production accelerating the process. These and other undesirable metabolites permeate and disrupt cell membranes, mitochondrial membranes, and nuclear membranes.
Incessant membrane damage results in cross-linkage or cleavage of proteins and lipoproteins, and oxidation of membrane lipids and lipoproteins. Cell permeability is diminished, intercellular ionic concentration increases, and cellular capacity to excrete or detoxify waste products is decreased. Waste products such as lipofuscin accumulate. The increase in intercellular ionic potassium concentration causes an increase in colloid density, and m-RNA and protein synthesis are hampered, resulting in decreased cellular repair. Some cells become so dehydrated they cannot function at all. Normal metabolic phosphorylation is gradually uncoupled, resulting in cell necrosis and apoptosis. Activation of transcription factors also elicts gene expression of collagenases which cause additional damage. The ultimate result of skin aging is that the regularity of tissue structure is lost. Individual cells enlarge, but the total number of cells decreases by at least approximately 30%. Intercellular collagen increases, and the proportion of soluble collagen decreases. Cross-linking between long-chain collagen macromolecules occurs. Elastin loses its discrete structure and elasticity, and has an increased calcium content. The dermis microscars and diminishes.
Sunlight and chemical exposure wreaks far greater destruction on the skin than time itself, and intensifies and augments the aging process. There is substantial evidence that ultraviolet radiation induces the formation of reactive oxygen species that trigger the pathways producing toxic intermediates, contributing to the overall metabolic changes described above (Ibbotson, S. H., et al., J. Investig. Derm. 112: 933–938, 1999; this paper and others, and the patents cited herein are expressly incorporated herein in their entireties by reference thereto). Damage to the surface of the skin from sun and chemical exposure is manifested as lines, mottling, discoloration, precancers and cancers.
Early suggestions for dealing with aging and inflammatory effects on skin were predominantly aimed at lubrications and emollients through use of topical compositions containing soothing agents, e.g., commercial hand lotion products. A bewildering variety of skin creams, lotions and ointments are now available over-the-counter, which typically either act to prevent water loss from the skin or to deliver nutrients into the dermal layers. More recently, attention has been directed to agents which address the underlying processes involved in skin damage, such as the underlying free radical generation processes. In this regard, investigations have been made with respect to the antioxidants vitamin E and vitamin C to quench free radicals on the surface of the skin and to protect lipid membranes intracellularly (Wilson, R., Drug and Cosmetic Industry, 32–34, 38, and 68, August 1992). Dermatological compositions suggested for the treatment of damaged and aging skin that directly counteract free radical generation metabolic sequelae include tocotrienol preparations (U.S. Pat. No. 5,545,398 to Perricone), precursors of acetylcholine such as dimethylamino-ethanol (U.S. Pat. No. 5,554,647 to Perricone), fatty acid esters of ascorbic acid such as ascorbyl palmitate (U.S. Pat. No. 5,574,063 to Perricone), fructose diphosphate (U.S. Pat. No. 6,051,244 to Perricone), catecholamines (U.S. Pat. No. 5,879,690 to Perricone), and polyenylphosphatidylcholine (U.S. Pat. No. 6,191,121 to Perricone).
Damaged skin may also be removed in chemical peels. Routine medical procedures typically involve the application of particular chemicals such as trichloroacetic acid, resorcinol or salicylic acid, followed by a short reaction time to allow the chemicals to interact with damaged skin areas. Several days later, the damaged areas peel off. Peels can be uneven, however, and sometimes cause other complications such as prolonged inflammation. Less stringent methods have been developed to remedy some of these problems, such as applying tricholoracetic acid with a surfactant and an emulsifier, and then irradiating to obtain a superficial peel (U.S. Pat. No. 4,874,361 to Obagi).
Thus, it would be desirable to provide an apparatus to effect mild alternative therapies for skin damage and aging, particularly for sun damage and wrinkles, that can be used instead of, or in addition to, other methods. It would be especially desirable to provide an apparatus to effect skin treatments that continuously counteract the action of proinflammatory and inflammatory cascades involved in inflammation and aging.